PROJECT SUMMARY/ABSTRACT The Molecular Oncology Program represents one of the two basic science fundaments to the University of California, Davis Comprehensive Cancer Center. The novel discoveries emanating from the program form the scientific underpinning of the translational and clinical cancer research to develop innovative modalities in the diagnosis and treatment of cancer. The two overarching topics of 1) Oncogenic Signaling and 2) Mechanisms of Genome Stability continue serving well to coalesce an eminent group of investigators into a cohesive program that through collaborations with one another and with numerous investigators in the other Cancer Center programs ensures that their discoveries are translated from the bench to the bedside. The Molecular Oncology Program strategically focuses on in vitro model systems leveraging the strength in biological research at UC Davis. This approach is complemented by associated in vivo studies using animal models conducted by the members in the Comparative Oncology Program. A significant pipeline of lead studies has been brought to clinical trials in cooperation with the Cancer Therapeutics and the Prostate Urothelial Cancer Program. Extending our strength in DNA repair to the analysis of cancer risk in human populations is the subject of collaborations with the Population Sciences & Health Disparities Program. A long- standing collaboration connects the studies in hormone receptor biology with translational and clinical studies in the Prostate Urothelial Cancer Program. The high-end technology and analysis tools developed and utilized by members in the Biomedical Technology Program enabled program members to better analyze molecular and cellular processes. SCIENTIFIC THEMES 1.Cytoplasmic Signaling and Chromosome Dynamics 2. Nuclear Signaling and Genome Stability ? Nuclear receptors and chromatin remodeling ? DNA repair and chromosome segregation ? Oncogenic signals transmitted to the nucleus ? Oncogenic signals emanating from the nucleus PROGRAM ASPECTS Co-leaders: Kermit Carraway, PhD, Wolf-Dietrich Heyer, PhD Members: 36 Total Grant Funding (ADC): $9.2 million Total Peer-Reviewed Funding (ADC): $8.7 million Total NCI funding (ADC): $2.7 million Total No. Publications: 464 Inter-programmatic publications: 102 (22%) Intra-programmatic publications: 47 (10%) Multi-institutional publications: 219 (47%) The membership of the Molecular Oncology Program remains at a dynamic steady state of 36 from 12 different department and 4 different schools at UC Davis, as well as LLNL. The total peer-reviewed, cancer-related funding (annual direct cost) has slightly declined to $9.2 million (from $10.8 million at the last competitive renewal) due to sequestration and the departure or retirement of several well-funded senior members. However, our NCI funding has even slightly increased (from $2.4 to $2.7 million) with 18 projects funded by NCI (17 at the last competitive renewal). The funding data exclude the HHMI funding of Dr. Hunter (~$1 million/yr direct cost) and VA funding to Dr. Chen ($191k/yr direct cost), effectively raising our total funding to $10.4 million, almost en par with our previous funding level. Typical for a basic science program, 20 of 36 members are located in basic sciences departments of the University of California, Davis, and their research in basic cancer biology is traditionally funded by NIHGMS. Since the summary funding report was assembled, one application received a fundable score (5%, NIGMS application to Dr. Roth), and Dr. Diaz obtained funding by the Whitehall Foundation with $225k/yr direct cost.